Diabetic Macular Edema
Conditions
Keywords
Diabetes Mellitus, Diabetic Retinopathy, Microneedle, Mircoinjection, Triamcinolone, Choroid, Choroid Injection, Aflibercept, Suprachoroidal, Triamcinolone acetonide
Brief summary
The purpose of this trial is to evaluate the safety and efficacy of suprachoroidal CLS-TA used with intravitreal aflibercept in subjects with DME.
Detailed description
This is a Phase 2, multicenter, randomized, double-masked, controlled, parallel-group study of 6 months duration in treatment-naïve subjects with DME. This study is projected to enroll approximately 60 subjects, randomly assigned 1:1 to one of two treatment groups. The study design includes up to 8 clinic visits over approximately 24 weeks. Subjects will attend visits for Screening (Visit 1, Days -30 to 0); Randomization and Baseline (Visit 2, Day 0 before dosing); Dosing and Evaluation (Visit 2 after dosing to Visit 5, Day 0 through Week 12); As-needed (PRN) Dosing and Follow up (Visit 6 through Visit 7, Week 16 through Week 20), and End of Study (Visit 8, Week 24).
Interventions
DRUGIVT aflibercept
IVT aflibercept \[2 mg/0.05 mL\]
DRUGSham SC
sham SC
DRUGSC CLS-TA
CLS-TA \[4 mg/100 μL\] SC injection
Sponsors
Clearside Biomedical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of type 1 or type 2 DM * DME with central involvement (\> 300 µm in the central subfield on spectral-domain optical coherence tomography \[SD-OCT\], in the study eye * ETDRS BCVA score of ≥ 20 letters read and ≤ 70 letters read in the study eye * Naïve to local pharmacologic treatment for DME in the study eye
Exclusion criteria
* IOP \> 21 mmHg in the study eye at Visit 1 (Day -30 to -1); subjects are not excluded if IOP is \<22 mmHg in the study eye with no more than 1 IOP lowering medication * Any previous treatment in the study eye with an ocular corticosteroid implant * Has significant media opacity precluding evaluation of retina and vitreous in the study eye. * History of glaucoma or optic nerve head change consistent with glaucoma damage * History of glaucoma surgery * History of clinically significant IOP elevation in response to corticosteroid treatment (steroid responder)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Best Corrected Visual Acuity Letter Score | Baseline, 6 months | Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured in the number of letters read correctly on an ETDRS eye chart. An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Central Subfield Thickness | Baseline, 6 months | Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A masked reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment will consist of IVT injection of Aflibercept followed by an SC injection of CLS-TA
IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\]
SC CLS-TA: SC CLS-TA \[40 mg/mL\] | 36 |
| Control Treatment will consist of IVT aflibercept injection followed by a sham SC procedure
IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\]
Sham SC: sham SC | 35 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Active | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 12 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 23 Participants | 48 Participants |
| Age, Continuous | 59.8 years STANDARD_DEVIATION 10.16 | 59.2 years STANDARD_DEVIATION 12.89 | 59.5 years STANDARD_DEVIATION 11.51 |
| Best corrected visual acuity | 57.1 letters STANDARD_DEVIATION 13 | 58.1 letters STANDARD_DEVIATION 11.33 | 57.6 letters STANDARD_DEVIATION 12.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 9 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 26 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 31 Participants | 32 Participants | 63 Participants |
| Region of Enrollment United States | 36 participants | 35 participants | 71 participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Male | 26 Participants | 24 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 36 | 0 / 35 |
| other Total, other adverse events | 10 / 36 | 11 / 35 |
| serious Total, serious adverse events | 6 / 36 | 4 / 35 |
Outcome results
Primary
Mean Change From Baseline in Best Corrected Visual Acuity Letter Score
Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured in the number of letters read correctly on an ETDRS eye chart. An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement.
Time frame: Baseline, 6 months
Population: The Intent-to-treat population included all randomized subjects who received at least 1 study treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active | Mean Change From Baseline in Best Corrected Visual Acuity Letter Score | 11.4 letters | Standard Error 1.63 |
| Control | Mean Change From Baseline in Best Corrected Visual Acuity Letter Score | 13.8 letters | Standard Error 1.59 |
Comparison: The primary efficacy analysis comparing ACTIVE with CONTROL on the mean change from baseline (Visit 2, Day 0) BCVA at Week 12 was be performed using a Mixed Model for Repeated Measurements (MMRM). This model included treatment (ACTIVE or CONTROL), visit (Visit 3 (Week 4), Visit 4 (Week 8), and Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20) and Visit 8 (Week 24), and the 2-way interactions of treatment and visit, and the BCVA baseline included as the covariate.p-value: 0.28890% CI: [-6.2, 1.4]Mixed model for repeat measures
Secondary
Mean Change From Baseline in Central Subfield Thickness
Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A masked reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema.
Time frame: Baseline, 6 months
Population: The Intent-to-treat population included all randomized subjects who received at least 1 study treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active | Mean Change From Baseline in Central Subfield Thickness | -212.1 microns | Standard Error 13.83 |
| Control | Mean Change From Baseline in Central Subfield Thickness | -178.6 microns | Standard Error 13.61 |